Vascular calcification by conventional X-ray and mortality in a cohort of predominantly African descent hemodialysis patients.

BACKGROUND/OBJECTIVE: There is a lack of studies describing the prevalence of vascular calcification (VC) and its association with mortality in maintenance hemodialysis (MHD) patients of African descent. We investigated if a VC score based on the number of calcified vascular beds was associated with mortality in MHD patients. METHODS: We analyzed data from 211 MHD patients enrolled from January 2010 to January 2011 in the prospective cohort study, "The Prospective Study of the Prognosis of Chronic Hemodialysis Patients (PROHEMO)," developed in Salvador, BA, Brazil. VC was evaluated using radiographs of the hands, abdomen, hip, and chest; the score was calculated by the number of calcified sites as 0 (absence of calcification), 1 (one calcified site), 2 (two sites), 3 (⩾3 sites). We used Cox's regression to estimate the hazard ratio (HR) and 95% confidence interval (CI) of associations between VC and mortality with adjustments for age and comorbidities. RESULTS: VC was detected in 114 (54.0%) patients; 37 (17.5%) with a VC score = 1; 21 (10%) with VC score = 2 and 56 (26.5%) with VC score = 3. Compared with VC score = 0, the adjusted hazard of death was 2.67 (95% CI: 1.12, 6.33) for patients with VC score = 1; HR = 2.89 (95% CI: 0.95, 7.63) for VC score = 2; and HR = 3.27 (95% CI: 1.47, 7.28) for VC score = 3. CONCLUSION: The present study in an African descent MHD population provides support for the VC score based on conventional radiography as a prediction tool for the clinical practice. As shown, the VC score was monotonically and independently associated with mortality.

Persistence of bone and mineral disorders 2 years after successful kidney transplantation.

BACKGROUND: Studies that have conducted bone biopsies after kidney transplantation are scarce, and the results are conflicting. METHODS: We evaluate the bone histomorphometry, in vitro proliferation, and alkaline phosphatase expression in osteoblasts isolated from bone biopsies from 27 kidney transplant patients. The patients had preserved renal function and were treated with the same immunosuppressive therapy, receiving a minimum dose of corticosteroids. RESULTS: The biochemical analysis revealed that 41% of the patients presented with hypercalcemia, 26% presented with hypophosphatemia, and hypovitaminosis D was detected in 63%. The histomorphometric analysis showed a reduced trabecular number and increased trabecular separation, mineral apposition rate, and mineralization lag time, as well as higher osteoid surface, osteoblastic surface, resorption surface, and osteoclastic surface and a lower mineralizing surface, compared with the controls. Based on the TMV classification, bone turnover was normal in 48%, high in 26%, and low in 26% of patients. Bone mineralization was delayed in 48% of the patients, and 58% of the patients with hypovitaminosis D presented with delayed bone mineralization. Bone volume was low in 37% of the patients. The osteoblasts from patients exhibited a higher degree of proliferation compared with those from controls. CONCLUSION: Eight-two percent of our patients presented with alterations in at least one of the TMV parameters. Persistence of hyperparathyroidism, hypovitaminosis D, and immunosuppressive drugs may have influenced osteoblast function, which would explain many of the bone alterations found in these patients.

First cytogenetic information for Drymoreomys albimaculatus (Rodentia, Cricetidae), a recently described genus from Brazilian Atlantic Forest.

The recently described taxon Drymoreomys albimaculatus is endemic to the Brazilian Atlantic Forest and its biology and genetics are still poorly known. Herein, we present, for the first time, the karyotype of the species using classical and molecular cytogenetics, which showed 2n=62, FN=62, and interstitial telomeric signals at the sex chromosomes. Nuclear and mitochondrial DNA sequences from the two karyotyped individuals verify the taxonomic identity as the recently described Drymoreomys albimaculatus and confirm the relationship of the species with other Oryzomyini. Additionally, external morphological information is provided.

Parathyroid hormone and phosphorus overload in uremia: impact on cardiovascular system.

BACKGROUND: Cardiac remodeling in uremia is characterized by left ventricular hypertrophy, interstitial fibrosis and microvascular disease. Cardiovascular disease is the leading cause of death in uremic patients, but coronary events alone are not the prevalent cause, sudden death and heart failure are. We studied the cardiac remodeling in experimental uremia, evaluating the isolated effect of parathyroid hormone (PTH) and phosphorus. METHODS: Wistar rats were submitted to parathyroidectomy (PTx) and 5/6 nephrectomy (Nx); they also received vehicle (V) and PTH at normal (nPTH) or high (hPTH) doses. They were fed with a poor-phosphorus (pP) or rich-phosphorus (rP) diet and were divided into the following groups: 'Sham': G1 (V+normal-phosphorus diet (np)) and 'Nx+PTx': G2 (nPTH+pP), G3 (nPTH+rP), G4 (hPTH+pP) and G5 (hPTH+rP). After 8 weeks, biochemical analysis, myocardium morphometry and arteriolar morphological analysis were performed. In addition, using immunohistochemical analysis, we evaluated angiotensin II, α-actin, transforming growth factor-beta (TGF-ß) and nitrotyrosine, as well as fibroblast growth factor-23 (FGF-23), fibroblast growth factor receptor-1 (FGFR-1) and runt-related transcription factor-2 (Runx-2) expression. RESULTS: Nx animals presented higher serum creatinine levels as well as arterial hypertension. Higher PTH levels were associated with myocardial hypertrophy and fibrosis as well as a higher coronary lesion score. High PTH animals also presented a higher myocardial expression of TGF-ß, angiotensin II, FGF-23 and nitrotyrosine and a lower expression of α-actin. Phosphorus overload was associated with higher serum FGF-23 levels and Runx-2, as well as myocardial hypertrophy. FGFR-1 was positive in the cardiomyocytes of all groups as well as in calcified coronaries of G4 and G5 whereas Runx-2 was positive in G3, G4 and G5. CONCLUSION: In uremia, PTH and phosphorus overload are both independently associated with major changes related to the cardiac remodeling process, emphasizing the need for a better control of these factors in chronic kidney disease.

The bone histology spectrum in experimental renal failure: adverse effects of phosphate and parathyroid hormone disturbances.

Bone disease is a common disorder of bone remodeling and mineral metabolism, which affects patients with chronic kidney disease. Minor changes in the serum level of a given mineral can trigger compensatory mechanisms, making it difficult to evaluate the role of mineral disturbances in isolation. The objective of this study was to determine the isolated effects that phosphate and parathyroid hormone (PTH) have on bone tissue in rats. Male Wistar rats were subjected to parathyroidectomy and 5/6 nephrectomy or were sham-operated. Rats were fed diets in which the phosphate content was low, normal, or high. Some rats received infusion of PTH at a physiological rate, some received infusion of PTH at a supraphysiological rate, and some received infusion of vehicle only. All nephrectomized rats developed moderate renal failure. High phosphate intake decreased bone volume, and this effect was more pronounced in animals with dietary phosphate overload that received PTH infusion at a physiological rate. Phosphate overload induced hyperphosphatemia, hypocalcemia, and changes in bone microarchitecture. PTH at a supraphysiological rate minimized the phosphate-induced osteopenia. These data indicate that the management of uremia requires proper control of dietary phosphate, together with PTH adjustment, in order to ensure adequate bone remodeling.

O hiperparatireoidismo secundário e a doença cardiovascular na doença renal crônica / Secondary hyperparathyroidism and cardiovascular disease in chronic kidney disease

Os pacientes portadores de doença renal crônica (DRC) apresentam elevado risco de complicações cardiovasculares (DCV). Esta associação foi primeiramente reconhecida nos pacientes em diálise, nos quais a incidência de morte por DCV é elevada. Nesses pacientes, fatores de risco nãotradicionais aliam-se aos tradicionais na promoção da DCV. Os distúrbios do metabolismo mineral são fatores de risco modificáveis, relacionados com calcificação vascular, mortalidade geral e cardiovascular. O mecanismo da calcificação vascular consiste em um processo ativo de precipitação de cálcio e fósforo e na presença de um desequilíbrio entre fatores estimuladores e inibidores da calcificação. A associação quer da remodelação óssea quer dosníveis séricos do PTH com a calcificação vascular não é clara. O efeito do PTH sobre o sistema cardiovascular não é explicado somente pela potencialização dos estados de hipercalcemia e hiperfosfatemia, ele atua na remodelação cardíaca e, portanto, sobre a morfologia e a função deste órgão.São necessários mais estudos para compreender o mecanismo fisiopatológico da DCV nos pacientes com DRC.

Adverse cardiovascular events are frequent complications of renal disease. This association was initially reported in end-stage renal disease patients inwhom cardiovascular death has a high frequency. In dialysis patients, non-traditional risk factors may act in concert with the traditional ones to the development of cardiovascular disease (CVD). Disorders of mineral metabolism are potentially modifiable and have been linked with cardiovascular outcomes indialysis population. Mechanisms involved in vascular calcification in CKD include active precipitation of calcium and phosphorus in the presence of markedly elevated extracellular concentrations, effect of calcification inducers or deficiency of inhibitors. The relationship between bone turnover and intact PTH concentration with vascular calcification were inconclusive. The adverse cardiovascular outcome in patients with high PTH concentrations is presumably not only explained by the association between PTH and high serum calcium and phosphorus concentrations. It also reflects direct adverse effects of PTH oncardiac function and morphology. The intrinsic effects of CKD on CVD risk profile are still unknown.